Designing a drug delivery system to target the eye is an interesting and challenging endeavor faced by scientists because of the critical and pharmacokinetically-specific environment that exists in the eye. Topical administration of ophthalmic drugs is used to alleviate the symptoms and signs caused by ocular surface inflammatory disorders, to treat infections, for glaucoma or intraocular inflammation (uveitis). However, the responsiveness toward the conventionally developed drug delivery system is limited because of the presence of several types of barriers in the eye that impede the effective passage of many drugs leading to minimal dose absorption. Ion activated in situ gelling ocular systems undergo phase transition in the presence of cations (present in the tear fluid), thus enhancing the residence time of drug in the cornea. In the present study natural polysaccharides (pectin alone or in combination with sodium alginate) or a pectin derivative (thiolated pectin [TP] alone or in combination with sodium alginate) were used to formulate in situ gelling eye drops. The formulations were evaluated for their gelling capacity, rheological studies, spreadability, bioadhesion strength, and in vitro drug release. Thiolation of pectin was observed to result in an increase in the gelling behavior, viscosity, and bioadhesive strength. The formulations comprising pectin alone (P7), combination of pectin and sodium alginate (P5SA1) or TP6 demonstrated good in vitro release characteristics. The optimized formulations displayed a significant decrease in the intraocular pressure as compared to the marketed formulation upon instillation in rabbit eye. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39788.